A Low-Carbohydrate Diet for Advanced or Metastatic Cancer

Trial Information

A Low-Carbohydrate Diet for Advanced or Metastatic Cancer

In their natural state within the body, cells normally depend on cellular respiration as the
source of energy and ATP. During times of complete or partial food deprivation these cells
can also rely on ketosis as an additional energy source. Tumor cells in contrast are
defective in this respect, lacking in the ability to utilize ketone bodies for energy and
instead are heavily dependent on glycolysis for their survival. Malignant cells depend
heavily on glycolysis for energy production even in high oxygen states. If the
investigators limit the supply of glucose, glycolysis would decrease and tumor cells would
lose their main source of energy supply.

In addition, increased carbohydrate intake is sensed by the pancreas and results in
increased insulin secretion. Insulin is important for normal growth in the body and is a
potent growth factor stimulating mitosis via signal transduction and DNA synthesis. It is a
potent growth factor which acts by binding to cell membrane insulin receptors and stimulates
mitosis via protein kinase B/Akt- mediated signal transduction and DNA synthesis.

Most human and mouse tumors take up more glucose than their surrounding normal tissue. By
using positron emission tomography with fluoro-deoxy-glucose, FDG-PET scans can be used to
detect and monitor tumor response to chemotherapy and radiation.

In this study, PET/CT scanning would be utilized to measure the amount of (at the screening
visit) glucose activity within certain tumors, before and after the diet.

Primary Aim: To determine the safety and tolerability of a modified low carbohydrate diet in
people with advanced cancer across different tumor types.

Hypothesi(e)s: The long term tolerability of the KD (Ketogenic Diet) has been established
(Groesbeck et al., 2006). Recent studies involving human patients with brain cancer showed
tolerability of the Ketogenic diet over a period as long as 19 months with minimal side
effects. However the MAD (Modified Atkins Diet) long term side effects are as of yet
unclear. Given the similarity of the MAD compared to the KD, and being less restrictive, the
long term side effects (kidney stones, dyslipidemia, gastroesophageal reflux) of the MAD is
projected to be similar, if not reduced, in comparison to the KD. Modified carbohydrate
diets as well as ketogenic diets have been tolerated by people with epilepsy. It is
hypothesized that the effect this diet will have on overall weight loss, hyperlipidemia, and
blood glucose levels will be minimal and tolerable even by cancer patients over a prolonged
period of time, up to 12 months or possibly longer. Given the tolerability of the diet in
brain cancer patients, it is hypothesized that patients with other types of tumors will find
this diet tolerable and safe.

Secondary Aims: To determine if quality of life is improved with the use of this diet. To
determine if the diet has any effect on tumor growth (size or spread) or to determine if
there is any effect on progression free survival (PFS) and overall survival (OS) of subjects
enrolled in the study.

Hypothesis(e): The diet showed good tolerance in human adult patient studies wherein the
diet was tolerated well up to 12 weeks in a group of diverse tumor types and up to more than
10 years in a glioma patient. It is hypothesized that cancer patients will be able to
tolerate this diet at 16 weeks or more. Studies in animals as well as in tumor tissue models
show slowing of tumor growth, and in some instances also showed tumor shrinkage. Human case
reports and a small study of 16 patients show tumor shrinkage and stable disease while on
the diet.

Inclusion Criteria

Subjects must meet all of the following criteria to be eligible for the study:

- 18 years of age or older.

- English speaking and written informed consent obtained.

- Patients presenting to the VAPHS Oncology inpatient or outpatient clinic with
cancer of advanced or metastatic stage.

- Must have measurable disease at least 1 cm in greatest diameter on CT or MRI
scanning. If a new FDG avid satellite lesions are noted this will be counted as
disease progression. The minimum size is 1 cm. The tumor will be measured at the
longest diameter. Either the primary tumor or metastatic tumor, either may be used.
In absence of primary tumor, we usually measure the next largest metastatic lesion.
The tumor will be chose by using RECIST criteria measure (at the screening visit)
tumors, then using the 4 response criteria, CR complete response= disappearance of
all target lesions, PR= 30% decrease in the sum of the longest diameter of target
lesions, PD progressive disease= 20% increase in the sum of the longest diameter of
target lesions, and SD stable disease= small changes that don't meet the above
criteria

- Patients must have solid, advanced or metastatic tumors, and have failed to respond
to chemotherapy or on chemotherapy holiday.

- Tumors must be PET positive in primary or metastatic site.

- Patients must not be actively receiving chemotherapy after holiday or have refused
or failed one or more prior chemotherapy or radiotherapy treatment.

- Subjects may be enrolled in any other studies as long as they are not under an active
form of chemotherapy or radiotherapy intervention.

- No subjects will be excluded based on their race, religion, ethnicity, and gender or
HIV status, as applicable.

Exclusion:

- Prisoners or subjects who are involuntarily incarcerated.

- Secondary brain metastases.

- History of Gout.

- AST or ATL > 1.5 X ULN.

- Creatinine > 2.0.

- Hematologic malignancies

- BMI < 22.

- History of kidney disease or kidney stones.

- Receiving chemotherapy including biologics.

- Recent AMI/TIA or stroke within one month of study entry.

- ECOG performance status of 3 or worse.

Type of Study:

Observational

Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Principal Investigator

Jocelyn Tan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

VA Pittsburgh Healthcare System

Authority:

United States: Federal Government

Study ID:

PRO00000367

NCT ID:

NCT01716468

Start Date:

October 2012

Completion Date:

December 2014

Related Keywords:

Cancer

Ketogenic Diet, Advanced Cancer, Neoplasm

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Location

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